Reduction in SIV replication in rhesus macaques infused with autologous lymphocytes engineered with antiviral genes.
Simian immunodeficiency virus (SIV) infection of nonhuman primates is one of the most relevant animals models of HIV infection in humans. To test a potential anti-HIV gene therapy strategy in this model, CD4-enriched lymphocytes from three rhesus macaques were subjected to retrovirally mediated gene transfer with a vector expressing an antisense tat/rev gene. This group of animals and three control macaques were subsequently infected with SIVmac239. Blood and lymph nodes from all macaques were sampled for more than a year to monitor the progress of infection. Although all animals became infected, the animals that received the lymphocytes engineered with the antisense vector demonstrated a significant reduction in viral load in both peripheral blood and lymph nodes, had sustained numbers of CD4+ cells, and exhibited little disruption of lymph node architecture.
Donahue
R E
RE
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, Maryland 20901, USA.
Bunnell
B A
BA
Zink
M C
MC
Metzger
M E
ME
Westro
R P
RP
Kirby
M R
MR
Unangst
T
T
Clements
J E
JE
Morgan
R A
RA
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D015694:Gene Products, rev; D015696:Gene Products, tat; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000494:pharmacology*; D008198:Lymph Nodes / Q000821:virology; D008253:Macaca mulatta / Q000821:virology*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000628:therapy; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
D000998:Antiviral Agents; D015694:Gene Products, rev; D015696:Gene Products, tat; D016376:Oligonucleotides, Antisense